January 14, 2005
Epi Update Managing Staff:
"The reason for collecting, analyzing and disseminating information on a disease is to control that disease. Collection and analysis should not be allowed to consume resources if action does not follow."
Foege WH., International
Journal of Epidemiology 1976; 5:29-37
Presenter: Roberta M. Hammond, Ph.D., Florida Department of Health Statewide Food and Waterborne Disease Coordinator, Bureau of Environmental Epidemiology
Date: Tuesday, January 25, 2005
Roberta Hammond is the
statewide food and waterborne disease coordinator at the Bureau of
Environmental Epidemiology at the Florida Department of Health in
Tallahassee. She can be reached at 850. 245.4116.
Fatal Rat-bite Fever in Florida and Washington, 2003
Fatal Rat-Bite Fever --- Florida and Washington, 2003
Rat-bite fever (RBF) is a rare, systemic illness caused by infection with Streptobacillus moniliformis. RBF has a case-fatality rate of 7%--10% among untreated patients (1). S. moniliformis is commonly found in the nasal and oropharyngeal flora of rats. Human infection can result from a bite or scratch from an infected or colonized rat, handling of an infected rat, or ingestion of food or water contaminated with infected rat excreta (1). An abrupt onset of fever, myalgias, arthralgias, vomiting, and headache typically occurs within 2--10 days of exposure and is usually followed by a maculopapular rash on the extremities (1). This report summarizes the clinical course and exposure history of two rapidly fatal cases of RBF identified by the CDC Unexplained Deaths and Critical Illnesses (UNEX) Project in 2003. These cases underscore the importance of 1) including RBF in the differential diagnoses of acutely ill patients with reported rat exposures and 2) preventing zoonotic infections among persons with occupational or recreational exposure to rats.
Florida. In early September 2003, a previously healthy woman aged 52 visited an emergency department (ED) with a 2-day history of headache, abdominal pain, diarrhea, lethargy, right axillary lymphadenopathy, progressive myalgias, and pain in her distal extremities. On physical examination, she was afebrile and hypotensive (blood pressure: 82/40 mmHg) with left-sided abdominal tenderness and scleral icterus; no rash was noted. Laboratory tests indicated a mildly elevated white blood cell count of 13,800 cells/µL (normal: 5,000--10,000 cells/µL), thrombocytopenia (71,000 platelets/µL [normal: 130,000--500,000 platelets/µL]), elevated alanine aminotransferase of 112 U/L (normal: 20--52 U/L), elevated aspartate aminotransferase of 154 U/L (normal: <40 U/L), elevated total bilirubin of 5.8 mg/dL (normal: 0.2--1.2 mg/dL), elevated blood urea nitrogen of 55 mg/dL (normal: 7--23 mg/dL), and elevated creatinine of 2.9 mg/dL (normal: 0.7--1.5 mg/dL).
The patient was admitted to the intensive care unit, where she became increasingly hypoxic with marked anemia (hemoglobin: 8.6 g/dL [normal: 12--16 g/dL]) and increasingly severe thrombocytopenia (32,000 platelets/µL). She was treated with ciprofloxacin, metronidazole, and vancomycin for possible gram-negative sepsis and received two blood transfusions; however, she died approximately 12 hours after admission. A maculopapular rash was noted postmortem. No autopsy was performed.
Peripheral blood smears obtained before death revealed abundant neutrophils and intracellular collections of filamentous bacteria (Figure). Premortem blood from a tube containing no additives or separators was inoculated onto a blood agar plate and incubated in CO2 at 95şF (35şC). After 72 hours, the culture demonstrated slight growth of gram-negative filamentous bacteria. UNEX was contacted for assistance, and diagnostic specimens were submitted to CDC for further laboratory evaluation. At CDC, the isolate was subcultured onto media enriched with 20% solution of sterile normal rabbit serum and incubated in a candle jar for 48 hours. Biochemical analyses identified the bacterial isolate as S. moniliformis. The 16S rRNA gene sequences amplified from DNA extracted from the patient's blood and the bacterial isolate were consistent with S. moniliformis.
The patient had been employed at a pet store. She was bitten on her right index finger by a rat in the store 2 days before symptom onset and 4 days before arriving at the ED. She self-treated the wound by using antiseptic ointment immediately after being bitten. In addition, she had regular contact with several pet rats, cats, a dog, and an iguana at her home; however, no bites from these animals were reported. None of the animals were tested for S. moniliformis.
Washington. In late November 2003, a previously healthy woman aged 19 years was pronounced dead on arrival at a hospital ED. No laboratory studies were performed in the ED. An acquaintance reported that the patient had experienced a 3-day history of fever, headache, myalgias, nausea, and profound weakness without cough, vomiting, diarrhea, or rash. Before her transport to the ED, she exhibited anxiety, confusion, and labored breathing. ED staff noted that she appeared jaundiced. The body was transported to the coroner's office, where an autopsy was performed.
Cultures of blood and tissue from autopsy were negative for pathogenic organisms. A toxicology screen was negative. Serologic assays for leptospirosis, Epstein-Barr virus, cytomegalovirus, and viral hepatitis were negative for recent infection. Histopathology revealed findings suggestive of a systemic infectious process that included disseminated intravascular coagulopathy and inflammatory cell infiltrates in the liver, heart, and lungs. UNEX was contacted for assistance, and project staff facilitated the submission of diagnostic specimens to CDC for further laboratory evaluation. Immunohistochemical assays performed at CDC for Leptospira spp., Bartonella quintana, spotted fever and typhus group rickettsiae, flaviviruses, hantaviruses, and influenza viruses were negative. Clusters of filamentous bacteria were identified in sections of the liver and kidney by using a silver stain. The 16S rRNA gene sequence amplified from DNA extracted from paraffin-embedded, formalin-fixed samples of liver and kidney was consistent with S. moniliformis.
The patient worked
as a dog groomer and lived in an apartment with nine pet rats. One pet rat
with respiratory symptoms had recently been prescribed oral doxycycline
after having been evaluated at a veterinary clinic. Doxycycline was
subsequently used to treat a second ill rat. None of the rats were tested
for S. moniliformis. The patient had no known animal bites during
the 2 weeks preceding her death.
Clinicians should consider RBF in the differential diagnosis for unexplained febrile illness or sepsis in patients reporting rat exposure. Initial symptoms might be nonspecific, but a maculopapular rash and septic arthritis commonly develop (1,5). However, as demonstrated by the cases in this report, patients can have severe disease before the onset of typical symptoms. Despite its name, approximately 30% of patients with RBF do not report having been bitten or scratched by a rat (1,5). Risk factors for RBF include handling rats at home and in the workplace (e.g., laboratories or pet stores). RBF is rare in the United States, with only a few cases documented each year (1,6,7). However, because RBF is not a nationally notifiable disease, its actual incidence has not been well described.
In the cases described here, diagnosis of RBF was delayed in part because of the inability to rapidly isolate or identify S. moniliformis. If infection with S. moniliformis is suspected, specific media and incubation conditions should be used (8). In the absence of a positive culture, identification of pleomorphic gram-negative bacilli in appropriate specimens might support a preliminary diagnosis (1). In the event of an unexplained death in a person with rat exposure, performing an autopsy might also be critical to identifying an etiology.
Because of the high prevalence of colonization and asymptomatic infection with S. moniliformis among rodents, testing and treatment of rats is not practical. Disease prevention should center on risk reduction among persons with frequent rat exposure. Adherence to simple precautions while handling rats can reduce the risk for RBF and other potential rodent-borne zoonotic infections, wound infections, and injuries. Persons should wear gloves, practice regular hand washing, and avoid hand-to-mouth contact when handling rats or cleaning rat cages (1,9). If bitten by a rat, persons should promptly clean and disinfect the wound, seek medical attention, and report their exposure history. A tetanus toxoid booster should be administered if >10 years have lapsed since the last dose (9,10).
Clinicians should contact their state health departments for assistance with diagnosis of unexplained deaths or critical illnesses and cases or clusters of suspected RBF or other zoonotic infections. UNEX coordinates surveillance for unexplained deaths possibly attributed to infection throughout the United States. Cases are reported by a network of health departments, medical examiners/coroners, pathologists, and clinicians. Epidemiologic and clinical data are collected, and available clinical and pathologic specimens are obtained for reference and diagnostic testing at state, CDC, and other laboratories. State and local health departments may contact UNEX for assistance with the evaluation of unexplained deaths that occur in their jurisdictions.
Contributors: WJ Pollock, MD, R Cunningham, Baptist Hospital; J Lanza, MD, S Buck, MD, PA Williams, Escambia County Health Dept, Pensacola; JJ Hamilton, MPH, R Sanderson, MA, Bur of Epidemiology, Florida Dept of Health. D Selove, MD, T Harper, Thurston County Coroner's Office; DT Yu, MD, Thurston County Dept of Health, Olympia; M Leslie, DVM, J Hofmann, MD, Washington Dept of Health. S Reagan, MPH, M Fischer, MD, A Whitney, MS, C Sacchi, PhD, P Levett, PhD, M Daneshvar, PhD, L Helsel, R Morey, Div of Bacterial and Mycotic Diseases; S Zaki, MD, C Paddock, MD, W Shieh, MD, J Sumner, J Guarner, MD, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; D Gross, DVM, EIS Officer, CDC.
Janet Hamilton, MPH, is
an Epidemic Intelligence Service fellow assigned to Escambia County. She
can be reached at 850.595.6267.
Infection Control Seminar to be Held in Tampa
Tampa Bay will host an
American Professionals in Infection Control (APIC) seminar on
January 28, 2005 titled "Infection Control, Moving Forward."
Contact hours (7.3) will be provided by St. Joseph Baptist Healthcare for nurses and laboratorians. The cost of registration for members of APIC is $45 and $55 for non-members. For further information, contact Cathy Ricchezza at Cathy.Ricchezza@baycare.org.
Jaime Forth is managing editor of Epi Update. She can be reached at 850.245.4444, ext. 2440.
Court Files Injunction Against
The Department of Defense had vaccinated over 1.25 million military men and women, emergency-essential personnel and mission-essential contractors against all forms of the disease since the FDA licensed it to do so in 1970. Military members who have already begun the vaccine series will remain in deferral status, although their immunity will not increase. Because the human body has immune memory, the next dose should receive a good antibody response when the anthrax vaccine is reintroduced.
The preliminary injunction, issued in December 2003, was based on the court's concern about the completeness of the FDA's approval process for the vaccine against inhalation anthrax. The second injunction, issued October 27, 2004 stated that the FDA's Final Rule and Final Order of December 2003 http://a257.g.akamaitech.net/7/257/2422/14mar20010800/edocket.access.gpo.gov/2004/pdf/03-32255.pdf. were insufficicient to support its conclusion that the vaccine should be approved for protection against inhaled anthrax. In short, the judge raised concerns about procedural issues, specifically the lack of a 90-day public comment period on the vaccine. The injunction did not address safety or the effectiveness of the vaccine.
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Pete Garner is
administrator of the Bureau of Epidemiology Surveillance Systems
Weekly Update: During the period January 2-8, 2005, the following arboviral activity (St. Louis encephalitis [SLE] virus, eastern equine encephalomyelitis [EEE] virus, Highlands J [HJ] virus, West Nile [WN] virus and dengue virus) was recorded for Florida:
West Nile (WN) virus activity: No counties have yet reported WN activity for 2005.
Eastern Equine Encephalomyelitis (EEE) virus activity: There were two seroconversions to EEE virus in sentinel chickens from Hillsborough and Volusia counties, both late 2004 bleed dates. In addition, a horse from Taylor County was confirmed with EEE illness onset of 12/06/04. No counties have yet reported EEE activity for 2005.
St. Louis Encephalitis (SLE) virus activity: None yet this year.
Highlands J (HJ) Virus activity: There were five seroconversions to HJ virus in sentinel chickens from Bay (1), Leon (3) and Walton (1) counties this week, all of them being counted as late 2004 seroconversions. No counties have reported 2005 HJ virus activity.
There are no counties currently under medical alert for mosquito-borne disease.
Cooler weather in many parts of the state is helping to reduce mosquito populations. Yet others are experiencing unseasonably warm weather favorable to mosquitoes. Where mosquitoes are present, people are urged to take precautions against getting bitten.
Dead birds should be reported to www.wildflorida.org/bird/. See the web page for more information: www.MyFloridaEH.com The Disease Outbreak Information Hotline offers recorded updates on medical alerts status and surveillance at 888.880.5782.
Click here to review the most recent disease figures provided by the Florida Department of Health Bureau of Epidemiology.
D'Juan Harris is a GIS
specialist in the Surveillance Systems Section of the Bureau of